Project Summary/Abstract Interest in global health among applicants to medical schools, residency programs, and infectious disease fellowships has grown enormously in recent years, but the career development pathways for translating this interest into successful academic careers remain poorly defined and perilous, with relatively few mentors available in academia. The candidate for this K24 Award renewal is a Professor of Pediatrics and Medicine who has established a successful research and mentoring program to investigate the immune response to childhood malaria and identify in vitro correlates of protective immunity among children in highly malaria endemic settings. This research program is based upon strong collaborative relationships with leading malaria epidemiologists and clinical trialists working in Uganda. The PI and her collaborators have forged an effective multidisciplinary team and have built substantial research infrastructure to conduct field studies in Tororo, Uganda, a setting of exceptionally high malaria transmission intensity. Malaria is the leading cause of pediatric deaths in Uganda and claims the life of one million children worldwide each year. The need for an effective vaccine against malaria is self-evident. However, the iterative process of vaccine development, refinement, and testing would be greatly aided by a better understanding of the immunologic effector mechanisms that confer protection from malaria, as well as immune subversion mechanisms that may hinder the development of durable immunity. The candidate has established a systematic approach to mentoring both pre-doctoral students and early career clinician-investigators engaged in patient-oriented research. Several trainees have obtained NIH K Award support, and some have recently assumed independent faculty positions at leading research institutions. Mentoring will be provided in the context of the candidate's own funded research program, which provides numerous opportunities for add-on projects initiated by trainees. The proposed studies will use samples and data from well-characterized pediatric cohorts in Uganda to identify correlates of protective immunity to malaria, and to determine how the natural acquisition of antimalarial immunity is altered by chemopreventive interventions and by prenatal exposure to malaria. In addition, this award will address fundamental questions regarding how fetal T cells respond to pathogen-derived antigens encountered in utero. The primary goal of this K24 will be to mentor young investigators with the skills required to conduct high quality translational immunology research, encourage their passion for patient-oriented global health research, and help them to become successful independent investigators. Specific mentoring emphases during the K24 renewal period will be on helping trainees to acquire the skills in bioinformatics and genomic data analysis that are needed for emerging high-parameter single cell immune profiling approaches (mass cytometry, single cell RNA sequencing), and to foster the careers of women, under-represented minorities, and investigators from low-resource countries to become successful academic faculty members.